Detecting ferroptosis and immune infiltration profiles in multiple system atrophy using postmortem brain tissue.

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Multiple system atrophy (MSA) involves α-synuclein aggregation and neurodegeneration.
• The roles of ferroptosis and immune responses in MSA pathogenesis are increasingly recognized.
• α-synuclein inclusions in oligodendrocytes characterize MSA.

Purpose of the Study:

• To investigate the association between ferroptosis, immune cell infiltration, and multiple system atrophy with cerebellar dysfunction (MSA-C).
• To identify potential diagnostic biomarkers for MSA-C using gene expression data.

Main Methods:

• RNA sequencing data from MSA-C patients and controls were analyzed.
• Weighted gene co-expression network analysis identified MSA-C-related gene modules.
• Machine learning identified ferroptosis-related genes, and CIBERSORT analyzed immune cell composition.

Main Results:

• Six MSA-C-related ferroptosis genes showed diagnostic value (AUC 0.662–0.791).
• MSA-C exhibited significantly higher proportions of CD8+ T cells (P=0.02) and resting NK cells (P=0.011) compared to controls.
• Gene Ontology and KEGG analyses predicted molecular functions related to these pathways.

Conclusions:

• Ferroptosis and T-cell infiltration are implicated as critical pathways in MSA-C development.
• Targeting ferroptosis and T-cell infiltration pathways may represent disease-modifying therapeutic strategies for MSA-C.